analyzing-functions-mast-cells-vivo-using-mast-cell-knock

Analyzing the Functions of Mast Cells <em>In Vivo</em> Using '<em>Mast Cell Knock-in</em>' Mice

Mast cells (MCs) are hematopoietic cells which reside in various tissues, and are especially abundant at sites exposed to the external environment, such ...

Stanford University School of Medicine

It has been suggested that mast cells might serve, under certain circumstances, as antigen-presenting cells (APCs) for T cells. However, whether cognate interactions between mast cells and class II-restricted CD4(+) T cells actually occur is still an open question. We addressed this question by using peritoneal cell-derived mast cells (PCMCs) and freshly isolated peritoneal mast cells as APC models. Our results show that in vitro treatment of PCMCs with interferon-gamma and interleukin-4 induced surface expression of mature major histocompatibility complex class II molecules and CD86. When interferon-gamma/interleukin-4-primed PCMCs were used as APCs for CD4(+) T cells, they induced activation of effector T cells but not of their naive counterparts as evidenced by CD69 up-regulation, proliferation, and cytokine production. Confocal laser scanning microscopy showed that CD4(+) T cells formed immunological synapses and polarized their secretory machinery toward both antigen-loaded PCMCs and freshly isolated peritoneal mast cells. Finally, on cognate interaction with CD4(+) T cells, mast cells lowered their threshold of activation via FcepsilonRI. Our results show that mast cells can establish cognate interactions with class II-restricted helper T cells, implying that they can actually serve as resident APCs in inflamed tissues.

Cell-cell cooperation at the T helper cell/mast cell immunological synapse.

Mast cells are key components of the skin microenvironment in psoriasis, yet their functional role in this T-cell-mediated inflammatory disorder remains to be elucidated.

Human mast cells drive memory CD4+ T cells toward an inflammatory IL-22+ phenotype.

Reply: To PMID 23518141.

Gouty arthritis is caused by the precipitation of monosodium urate monohydrate (MSU) crystals in the joints. While it has been reported that mast cells (MCs) infiltrate gouty tophi, little is known about the actual roles of MCs during acute attacks of gout. This study was undertaken to assess the role of MCs in a mouse model of MSU crystal-induced acute arthritis.

Contribution of mast cell-derived interleukin-1β to uric acid crystal-induced acute arthritis in mice.

Mast cells are tissue-resident immune cells that play a key role in inflammation and allergy. Here we show that interaction of mast cells with antibody-targeted cells induces the polarized exocytosis of their granules resulting in a sustained exposure of effector enzymes, such as tryptase and chymase, at the cell-cell contact site. This previously unidentified mast cell effector mechanism, which we name the antibody-dependent degranulatory synapse (ADDS), is triggered by both IgE- and IgG-targeted cells. ADDSs take place within an area of cortical actin cytoskeleton clearance in the absence of microtubule organizing centre and Golgi apparatus repositioning towards the stimulating cell. Remarkably, IgG-mediated degranulatory synapses also occur upon contact with opsonized Toxoplasma gondii tachyzoites resulting in tryptase-dependent parasite death. Our results broaden current views of mast cell degranulation by revealing that human mast cells form degranulatory synapses with antibody-targeted cells and pathogens for dedicated secretion and defence.

Nicolas Gaudenzio

Department of Pathology

Stanford University School of Medicine

Analyzing the Functions of Mast Cells In Vivo Using 'Mast Cell Knock-in' Mice